DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-3, 7-10, and 18-19, of record 12/31/2025, are pending and subject to prosecution. Claims 1-3, 7, and 10 are amended.
Status of Prior Rejections/Response to Arguments
RE: Objection to the specification:
The submission of a substitute specification is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claims 1-3, 7-10, and 18-19 under 35 U.S.C. 112(b):
The amendments to claims 1, 7, and 10 are effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claims 1-2, 7-10, and 18-19 under 35 U.S.C. 103 over Brüstle et al. (Science, 1999) in view of Fults et al. (Neoplasia, 2002) and Neumann et al. (Nature Aging, 2021), evidenced by Goldman et al. (Development, 2015):
RE: Rejection of claims 1-3, 7-10, and 18-19 under 35 U.S.C. 103 over Brüstle et al. (Science, 1999) in view of Fults et al. (Neoplasia, 2002) and Neumann et al. (Nature Aging, 2021), of record in IDS filed 12/19/2022, evidenced by Goldman et al. (Development, 2015), of record in IDS filed 12/19/2022, further in view of Cambier et al. (US 20070116691 A1):
RE: Provisional rejection of claims 1-2, 8-9, and 18-19 on the ground of nonstatutory double patenting over claims 1, 3-4, 8, 10-14, and 18-19 of co-pending Application No. 19151811:
The amendment of claim 1 to delete the MYC gene is effective to obviate the rejections. The rejections are withdrawn.
New/Maintained Rejections
Election/Restrictions
Applicant’s election without traverse of the combination of CEBPZ, MYBL2, NYFB, and TFD1 as the species in the reply filed on 9/30/2025 has been acknowledged. The elected species (a method of rejuvenating glial cells of the brain and/or brain stem in a subject, said method comprising: introducing the population of genetically modified glial progenitor cells into the brain and/or brain stem of the subject, wherein the genetically modified glial progenitor cells have increased expression of one or more genes compared to the same type of glial progenitor cells that have not been genetically modified, wherein the one or more genes are CEBPZ, MYBL2, NFYB, and TFDP1, and wherein said increased expression of the one or more genes in the genetically modified glial progenitor cells confer competitive advantage over native or already resident glial progenitor cells in the subject) is free of the prior art. The search has been expanded to additional species, specifically, genetically modified glial progenitor cells that have increased expression of MYBL2. Claims 1-3, 7-10, and 18-19 read on the additional species and have been examined on the merits.
Claim Interpretation
The limitation “competitive advantage” is interpreted as encompassing the preferential proliferation, population expansion, durable survival, and/or stable integration of a cell population placed in apposition to or admixture with a genetically and/or epigenetically-distinct cell population, to the detriment and eventual partial or complete replacement of the latter, consistent with ¶0054 of the instant application’s PG Pub.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 7-10, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Brüstle et al. (Science, 1999) in view of Raschella et al. (Journal of Biological Chemistry, 1995).
Regarding claims 1-2 and 7: Brüstle et al. teach the transplantation of ESC-derived glial precursors (which reads on “glial progenitor cells”) into mouse brains (which reads on “introducing… into the brain”) (See Abstract). Brüstle et al. do not teach the cells as being genetically modified to have increased MYBL2 expression.
Raschella et al. teach a requirement for B-myb (which reads on “MYBL2”) for the survival (which reads on “competitive advantage”) of neuroblastoma cells (See Abstract and page 8543, col. 1, ¶1). Transfection with an antisense polynucleotide targeting B-myb reduced clone number (See table 1). Constitutive overexpression of B-myb did not increase cell proliferation, however, the cells already had a high endogenous levels of B-myb (See page 8543, col. 1, full ¶3). Raschella et al. also teach that that overexpression of B-myb is associated with proliferation of other cell types (See page 8540, col. 2, full ¶2).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Brüstle et al. to comprise genetic modification of the glial precursor cells with the B-myb vector taught by Raschella et al. One would be motivated to make this modification because Raschella et al. teach that B-myb is required for the survival of one type of neural cell, a LAN-5 neuroblastoma cell line (See Abstract; page 8543, col. 1, ¶1; and table 1), which suggests that increased B-myb expression may promote survival of other neural lineage cells. Additionally, Raschella et al. teach that that overexpression of B-myb is associated with proliferation of other cell types (See page 8540, col. 2, full ¶2). There would be a reasonable expectation of success in making this modification because the B-myb expression vector of Raschella et al. could be readily used with the cells of Brüstle et al.
Regarding claims 8-9 and 18-19: Following the discussion of claims 1-2 and 7, Brüstle et al. do not expressly teach the transplantation of human ESC-derived cells into a human subject. However, Brüstle et al. teach that the use of autologous ESC-derived glial cells may be possible for the treatment of human neurological disorders (See page 756, col. 1, full ¶1). It would have therefore been obvious to modify the method of Brüstle et al. to comprise the generation of glial precursor cells from human ESCs for transplantation into the brains of human subjects. One would be motivated to make this modification for treating human neurological disorders, and the process could be done in a similar manner as had been demonstrated with mice.
Regarding claim 10: Following the discussion of claims 1-2 and 7, Brüstle et al. teach that the engraftment and proliferation of the transplanted cells may eliminate undesired cells in the donor cell population (which reads on “said introducing results in replacement of the native or already resident glial cells”) (See page 755, col. 3, ¶1 and page 756, col. 1, ¶1).
Claims 1-3, 7-10, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Brüstle et al. (Science, 1999) in view of Raschella et al. (Journal of Biological Chemistry, 1995), further in view of Tanaka et al. (US 20160187319 A1).
The teachings of Brüstle et al. and Raschella et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 3: Following the discussion of claims 1-2, 7-10, and 18-19, Brüstle et al., modified by Raschella et al., render obvious the transplantation of glial precursor cells overexpressing MYBL2 but do not expressly teach the sequence of SEQ ID NO 5.
Tanaka et al. teach a sequence for the human anti-apoptosis-related protein MYBL2, SEQ ID NO 77, that encodes a sequence identical to the sequence of instant SEQ ID NO 5 (See 0086 and 0107, SEQ ID NO 78, and alignment below (first 120 aa displayed)).
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It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method rendered obvious by Brüstle et al., modified by Raschella et al., to substitute the MYBL2 nucleotide sequence taught by Tanaka et al. Substitution of one known element for another known element is considered to be prima facie obvious, absent a showing that the substitution yields more than expected results. See MPEP 2143(I)(B).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633